This invention relates to the manufacture of N-acetyl-p-aminophenol and more particularly to a improved process in which N-acetyl-p-aminophenol is prepared by acetylation of p-aminophenol that has been produced by catalytic hydrogenation of nitrobenzene in acidic aqueous medium.
N-acetyl-p-aminophenol ("APAP") is an analgesic more commonly known as acetaminophen. Conventionally, APAP is produced by acetylation of p-aminophenol ("PAP") with acetic anyhydride. In one variation of this process, the PAP used is produced by catalytic hydrogenation of nitrobenzene in an acidic aqueous medium, for example, in approximately 10% to 15% by weight solution of sulfuric acid.
According to conventional practice, the PAP is first isolated from the hydrogenation reaction medium through precipitation with a base, and the precipitate taken up in a solvent prior to acetylation. Precipitation and redissolution of the PAP has been considered necessary in order to exclude impurities from the acetylation reaction medium. Among the impurities typically present in the PAP reaction liquor are aniline, o-aminophenol, 4,4'-diaminodiphenylether, and other aromatic amines at trace or low levels. Purification of the crude PAP system is necessary to provide for satisfactory manufacture of U.S.P. quality APAP.
In the co-pending and co-assigned application of Clingan et al., Ser. No. 251,461, filed Apr. 20, 1981, U.S. Pat. No. 4,440,954, a process is disclosed for removing 4,4'-diaminodiphenylether from the PAP hydrogenation liquor by extraction with a mixture of aniline and toluene. While this process is quite effective for removing the 4,4'-diaminodiphenylether, residual aniline content in the extract is typically in the range of 25 g/L to 45 g/L. In implementation of the Clingan et al. process, therefore, it has still been considered essential to precipitate PAP from the raffinate by treatment with base, separate the PAP by centrifugation or filtration, and wash the filter cake prior to acetylation.